Abstract
Compliance to present AD medications is rather low due to adverse side effects (nausea, vomitting, diarrhea) and limited efficacy of cholinesterase inhibitors and nicotinic receptor sensitizing agents (APL). Efficacy and side effect profile of galantamine can dramatically be improved by administration as pro-drug. A series of novel derivatives of galantamine (pro-drugs) were synthesized and tested in pharmacokinetic and animal model studies for efficacy in cognitive tests, and for adverse effects. For selected pro-galantamines we observed dramatically improved brain-to-blood ratios, rapid enzymatic cleavage to galantamine and full reactivity of the drug. Using the scopolamine-T-Maze mouse model, increased efficacy when applied as pro-drug was observed. In the ferret dramatically reduced emetic responses were observed when the drug was administered as pro-galantamine rather than as galantamine. Our pro-galantamines constitute a novel and advantageous drug treatment for Alzheimer's disease. Due to the dramatically reduced side effects profile, pro-galantamines may be administered immediately at the efficaceous dose rather than by cautious months-long up-titration to this dose. Together with improved efficacy, these properties may dramatically enhance patients' and caretakers' acceptance of this drug.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
